Trial reportClinical and translational science2019
Does In Vitro Cytochrome P450 Downregulation Translate to In Vivo Drug-Drug Interactions? Preclinical and Clinical Studies With 13-cis-Retinoic Acid.
Trial report in Clinical and translational science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Impact of Pregnancy and Vitamin A Supplementation on CYP2D6 Activity.Journal of clinical pharmacology · 2023Trial
- Role of metabolites in drug-drug interactions.Drug metabolism and pharmacokinetics · 2026Review
- Comprehensive proteome profiling of cytochrome P450 isoforms in cancer models.Clinical proteomics · 2025Article
- Application of a mouse model humanized for cytochrome P450-mediated drug metabolism to predict drug-drug interactions between a peptide and small molecule drugs.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- The strong clinical interaction between bupropion and CYP2D6 is primarily mediated through bupropion metabolites and their stereoisomers: A paradigm for evaluating metabolites in drug-drug interaction risk.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- The interplay between retinoic acid binding proteins and retinoic acid degrading enzymes in modulating retinoic acid concentrations.Current topics in developmental biology · 2025Review
- LX-2 Stellate Cells Are a Model System for Investigating the Regulation of Hepatic Vitamin A Metabolism and Respond to Tumor Necrosis FactorDrug metabolism and disposition: the biological fate of chemicals · 2024Article
- Effect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne.British journal of clinical pharmacology · 2024Article
- CYP2D6 Activity Is Correlated with Changes in Plasma Concentrations of Taurocholic Acid during Pregnancy and Postpartum in CYP2D6 Extensive Metabolizers.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- A case of chronic granulomatous disease and acne: is isotretinoin a safe treatment?Dermatology reports · 2023Article
- Isotretinoin and its Metabolites Alter mRNA of Multiple Enzyme and Transporter Genes In Vitro, but Downregulation of Organic Anion Transporting Polypeptide Does Not Translate to the Clinic.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Infant Dextromethorphan and Dextrorphan Exposure via Breast Milk From Mothers Who Are CYP2D6 Extensive Metabolizers.Journal of clinical pharmacology · 2022Article
- Plasma Retinoid Concentrations Are Altered in Pregnant Women.Nutrients · 2022Article
- Clozapine modulates retinoid homeostasis in human brain and normalizes serum retinoic acid deficit in patients with schizophrenia.Molecular psychiatry · 2021Article
- Biochemical and physiological importance of the CYP26 retinoic acid hydroxylases.Pharmacology & therapeutics · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
All-trans-retinoic acid (atRA) downregulates cytochrome P450 (CYP)2D6 in several model systems. The aim of this study was to determine whether all active retinoids downregulate CYP2D6 and whether in vitro downregulation translates to in vivo drug-drug interactions (DDIs). The retinoids atRA, 13cisRA, and 4-oxo-13cisRA all decreased CYP2D6 mRNA in human hepatocytes in a concentration-dependent manner. The in vitro data predicted ~ 50% decrease in CYP2D6 activity in humans after dosing with 13cisRA. However, the geometric mean area under plasma concentration-time curve (AUC) ratio for dextromethorphan between treatment and control was 0.822, indicating a weak induction of dextromethorphan clearance following 13cisRA treatment. Similarly, in mice treatment with 4-oxo-13cisRA-induced mRNA expression of multiple mouse Cyp2d genes. In comparison, a weak induction of CYP3A4 in human hepatocytes translated to a weak in vivo induction of CYP3A4. These data suggest that in vitro CYP downregulation may not translate to in vivo DDIs, and better understanding of the mechanisms of CYP downregulation is needed.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.